1. Field of the Invention
The invention relates generally to methods and kits useful for detecting, diagnosing or evaluating cancer and more specifically to methods and kits for detecting, diagnosing or evaluating ovarian cancer by detecting methylation changes in nucleic acid samples of subjects with a profile of gene markers.
2. Background Information
Ovarian cancer is the second most common gynecological cancer and the leading cause of death among gynecological cancers worldwide. Approximately 21,650 new cases were detected in 2008 in the United States, leading to approximately 15,520 deaths from this cancer. Seventy percent of patients with ovarian cancer have advanced disease (stage II or IV) at presentation, with a 5-year survival rate of 15 to 20% despite aggressive treatment, while patients presenting with early disease have a survival rate above 90%. The high mortality of ovarian cancer is related to the absence of symptoms in the majority of the cases during the early stages of the disease, and also to the lack of truly sensitive and specific screening techniques. The best studied serum biomarker for ovarian cancer is CA-125, which is elevated in approximately 80% of women with advanced disease, but only 50-60% in patients with early-stage disease.
It has been shown that genetic and epigenetic changes contribute to the development and progression of tumor cells. Epigenetic alterations in promoter methylation and histone acetylation have been associated with cancer-specific expression differences in human malignancies. Methylation has been primarily considered as a mechanism of tumor suppressor gene (TSG) inactivation, and comprehensive whole-genome profiling approaches to promoter hypermethylation have identified multiple novel putative TSGs silenced by promoter hypermethylation.
Understanding the epigenetic changes that lead to cancer progression will help unravel key biologic processes that lead to cancer formation. Thus, there is an imperative need to find new molecular markers that will: a) help determine the risk of developing cancer to consider appropriate preventive interventions; b) help detect cancers early when they are amenable to surgical cure; c) help to predict response of a particular therapy (such as paclitaxel); and d) help to determine the overall outcome of a cancer patient.